The investigators propose to address the hypothesis that pregnancy decreases vascular tone and reactivity by enhancing estradiol-sensitive endothelium-dependent mechanisms. Specifically, they hypothesize that estradiol induces endothelial and smooth muscle enzymes whose actions decrease vascular tone and reactivity. Thus, variation in organ sensitivity to estradiol ultimately determines the redistribution of blood flow during pregnancy. The investigators propose to study the effect of pregnancy and estradiol on enzymes responsible for modulating vascular reactivity via either cGMP or cAMP using pregnant, nonpregnant, and estradiol-treated castrate guinea pigs. Four specific aims will be addressed: 1) determine the effect of pregnancy and estradiol on the location and transcription of elements critical for modulating vascular reactivity; 2) determine the effect of pregnancy and estradiol on the specific activity of enzymes important in modulating vascular reactivity; 3) determine the effect of pregnancy and estradiol on G-protein coupled vascular responses; and 4) determine whether pregnancy alters endothelial function in resistance vessels.